scholarly journals Whole-exome sequencing identification of novel DNAH5 mutations in a young patient with primary ciliary dyskinesia

2016 ◽  
Vol 14 (6) ◽  
pp. 5077-5083 ◽  
Author(s):  
Gen Kano ◽  
Hisashi Tsujii ◽  
Kazuhiko Takeuchi ◽  
Kaname Nakatani ◽  
Makoto Ikejiri ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Young Patient ◽  
Whole Exome Sequencing ◽  
Primary Ciliary Dyskinesia ◽  
Whole Exome ◽  
Ciliary Dyskinesia

scholarly journals Whole-exome sequencing accuracy in the diagnosis of primary ciliary dyskinesia

2020 ◽  
Vol 6 (4) ◽  
pp. 00213-2020
Author(s):  
Alex Gileles-Hillel ◽  
Hagar Mor-Shaked ◽  
David Shoseyov ◽  
Joel Reiter ◽  
Reuven Tsabari ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Primary Ciliary Dyskinesia ◽  
Diagnostic Yield ◽  
Characteristic Curve ◽  
Transmission Electron Microscopy Analysis ◽  
Alternative Diagnosis ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Ciliary Dyskinesia

The diagnosis of primary ciliary dyskinesia (PCD) relies on clinical features and sophisticated studies. The detection of bi-allelic disease-causing variants confirms the diagnosis. However, a standardised genetic panel is not widely available and new disease-causing genes are continuously identified.To assess the accuracy of untargeted whole-exome sequencing (WES) as a diagnostic tool for PCD, patients with symptoms highly suggestive of PCD were consecutively included. Patients underwent measurement of nasal nitric oxide (nNO) levels, ciliary transmission electron microscopy analysis (TEM) and WES. A confirmed PCD diagnosis in symptomatic patients was defined as a recognised ciliary ultrastructural defect on TEM and/or two pathogenic variants in a known PCD-causing gene.Forty-eight patients (46% male) were enrolled, with a median age of 10.0 years (range 1.0–37 years). In 36 patients (75%) a diagnosis of PCD was confirmed, of which 14 (39%) patients had normal TEM. A standalone untargeted WES had a diagnostic yield of 94%, identifying bi-allelic variants in 11 known PCD-causing genes in 34 subjects. A nNO<77 nL·min was nonspecific when including patients younger than 5 years (area under the receiver operating characteristic curve (AUC) 0.75, 95% CI 0.60–0.90). Consecutive WES considerably improved the diagnostic accuracy of nNO in young children (AUC 0.97, 95% CI 0.93–1). Finally, WES established an alternative diagnosis in four patients.In patients with clinically suspected PCD and low nNO levels, WES is a simple, beneficial and accurate next step to confirm the diagnosis of PCD or suggest an alternative diagnosis, especially in preschool-aged children in whom nNO is less specific.

scholarly journals Whole Exome Sequencing Accuracy in the Diagnosis of Primary Ciliary Dyskinesia

2020 ◽  
Author(s):  
A. Gileles-Hillel ◽  
D. Shoseyov ◽  
J. Reiter ◽  
R. Tsabari ◽  
M. Cohen-Cymberknoh ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Primary Ciliary Dyskinesia ◽  
Whole Exome ◽  
Ciliary Dyskinesia

scholarly journals Pathogenic variants identified using whole-exome sequencing in Chinese patients with primary ciliary dyskinesia

2021 ◽  
Author(s):  
Yutian Ye ◽  
Qijun Huang ◽  
Lipeng Chen ◽  
Chunxian Liang ◽  
Kaixue Zhuang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Primary Ciliary Dyskinesia ◽  
Rare Variants ◽  
Genetic Disorders ◽  
Autosomal Recessive Disorder ◽  
Bioinformatic Analysis ◽  
Chinese Patients ◽  
Whole Exome ◽  
Ciliary Dyskinesia

Abstract Background Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder. The genetic factors contributing to PCD pathogenesis remain elusive for approximately 20–35% of patients with complex and abnormal clinical phenotypes. Our study aimed to identify causative variants of sporadic PCD genes using whole-exome sequencing (WES). Result All patients were diagnosed with PCD based on clinical phenotype or transmission electron microscopy (TEM) images of cilia. WES and bioinformatic analysis were then conducted for patients with PCD. Identified candidate variants were validated by Sanger sequencing. Pathogenicity of candidate variants was then evaluated using in silico software and the American College of Medical Genetics and Genomics (ACMG) database. In total, 15 rare variants were identified in five patients with PCD. Five new variants of CCDC40, DNAH1, DNAAF3, and DNAI1 were considered causative variants and included one splicing and three homozygous variants. Conclusion Our study demonstrated that patients with PCD carry rare causative variants of multiple genes. Our findings indicated that not only known causative genes but also other functional genes should be considered for heterogeneous genetic disorders.

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